Atherosclerosis is an artery disease believed to arise from endothelial malfunction, accumulation of lipid materials in the intima of artery, inflammatory cell infiltration and reaction, artery wall structure damage, smooth muscle cell proliferation and fibrosis change. These factors may result in artery stenosis and ischemia of supplied organs and severe clinical consequences, such as heart attack in coronary artery stenosis, claudication and critical limb ischemia in occlusive peripheral vascular disease.
Atherosclerosis may be treated by atherectomy (e.g., removal of stenosed tissue). For example, directional atherectomy may use a catheter-based system to excise and retrieve plaque tissue for the transluminal treatment of coronary and peripheral atherosclerotic artery disease. The excision and collection of plaque tissue in directional atherectomy not only leaves behind a large and smooth lumen at the treated artery segment, but may also provide plaque tissue for histopathological analysis and new insights into the mechanism of atherosclerotic progress and variable therapy response.
Atherosclerotic stenoses in coronary and peripheral arteries vary widely in presentation and severity. In peripheral arteries the disease is under-diagnosed and under-treated, amputation rate in the US is staggering at 200,000 per year and recurrence rates following peripheral interventions (atherectomy, angioplasty and stenting) are still high. Peripheral stent fracture and failure of drug eluding stents in the periphery remains a big problem. The Baim-Kuntz coronary model of “bigger is better” has been difficult to apply to peripheral vessels because of the diffuse nature of the disease and the large atherosclerotic burden. A high capacity atherectomy system with on-board real-time imaging to guide plaque resection could potentially overcome the disadvantages in current devices and allow the Baim-Kuntz model to be applied to the peripheral vascular space for the first time.
As mentioned above it is well recognized that peripheral plaque burden is large in comparison to coronary lesions. Current atherectomy systems leave up to 60% of the atheroma atheroma in the vessel as confirmed by intra-vascular intra-sound (IVUS). A new image guided atherectomy (IGA) system with greater capacity for tissue management may be better able to safely achieve maximal luminal gain with minimal barotraumas. To achieve this improved acute outcome, a new cutter design combined with imaging near the cutter edge may be used. The method and devices described herein may help guide treatment with such a device, or even in devices that do not include cutting components and/or on-board imaging.
Despite high procedure success rates, excellent patency rate, and low complications, post-intervention restenosis often limits plaque excision methods from becoming a more routine and effective resvasculization procedure for the treatment of coronary and peripheral atherosclerotic artery disease. Thus, there is a need to understand the mechanism of restenosis, and to determine new approaches for preventing and treating post-intervention restenosis.
Although there have been other attempts to histopathologically analyze excised atherosclerotic plaque tissue, the results have generally proven unsatisfactory. For example, the relationship between plaque histopathological components and subsequent restenosis atherosclerotic lesions treated with directional atherectomy device has been controversial. Such plaque histopathological studies and evaluations have been mostly based only on the qualitative presence or absence of different plaque components. Quantitative histological analysis may provide more detail information to help understand the mechanism of restenosis. Herein we describe a method of describing and quantifying various atherosclerotic plaque elements, and devices for applying this analysis. Furthermore, we herein identify specific factors and parameters that correlate with angiographic restenosis rates in coronary atherosclerotic patients treated by directional atherectomy.
We have discovered that histopathological analysis of atherosclerotic artery tissue from patients with cardiovascular disease may be used to predict incidence of restenosis in the artery. More particularly, restenosis of may be predicted based on the histopathological analysis of atherosclerotic tissue (including excised fragments from atherectomy procedures) in patients with atherosclerotic artery disease. The histopathological analysis applied may be quantitative; furthermore, quantitative estimates and ranges are provided which may correlate to restenosis. Applications of the quantitative histological parameters and ranges of values of these parameters are also described.